E2F integrates cell cycle progression with DNA repair, replication, and G 2 /M checkpoints
Open accessAbstract
The E2F transcription factor family is known to play a key role in the timely expression of genes required for cell cycle progression and proliferation, but only a few E2F target genes have been identified. We explored the possibility that E2F regulators play a broader role by identifying additional genes bound by E2F in living human cells. A protocol was developed to identify genomic binding sites for DNA-binding factors in mammalian cells that combines immunoprecipitation of cross-linked protein–DNA complexes with DNA microarray analysis. Among ∼1200 genes expressed during cell cycle entry, we found that the promoters of 127 were bound by the E2F4 transcription factor in primary fibroblasts. A subset of these targets was also bound by E2F1. Most previously identified target genes known to have roles in DNA replication and cell cycle control and represented on the microarray were confirmed by this analysis. We also identified a remarkable cadre of genes with no previous connection to E2F regulation, including genes that encode components of the DNA damage checkpoint and repair pathways, as well as factors involved in chromatin assembly/condensation, chromosome segregation, and the mitotic spindle checkpoint. Our data indicate that E2F directly links cell cycle progression with the coordinate regulation of genes essential for both the synthesis of DNA as well as its surveillance.
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Previous global ChIP/microarray studies suggested that E2Fs can bind the MAD2 promoter in normal fibroblasts.
“Concordantly, previous global chromatin immunoprecipitation/microarray studies suggested that E2Fs can bind the MAD2 promoter in normal fibroblasts 14 .”
From Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control (2004) · cites this paper as [14]
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- Authors
- Ren, B., Cam, H., Takahashi, Y., Volkert, T., Terragni, J., Young, R. A., & Dynlacht, B. D.
- Affiliations
- Harvard University (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2002-01-15
- Volume
- 16
- Issue
- 2
- Pages
- 245-256
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC155321
- OpenAlex
- W2132786809
- Cited by
- 1,125
- References
- 39
- Citations by year
- 2026: 18 · 2025: 32 · 2024: 32 · 2023: 30 · 2022: 44 · 2021: 38 · 2020: 38 · 2019: 33 · 2018: 42 · 2017: 26 · 2016: 18 · 2015: 35 · 2014: 33 · 2013: 24 · 2012: 35
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- Helen Hay Whitney Foundation
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- E2F transcription factors, E2F4, E2F1, cell cycle progression, DNA repair, DNA replication, G2/M checkpoint, DNA damage checkpoint, mitotic spindle checkpoint, chromatin assembly, chromosome segregation, E2F target genes, promoter binding sites, chromatin immunoprecipitation, DNA microarrays, primary fibroblasts
- MeSH terms
- DNA Damage, DNA Repair, DNA Replication, DNA-Binding Proteins, Humans, Mitosis, Precipitin Tests, Transcription Factors, G2 Phase, Cell Cycle Proteins, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, E2F Transcription Factors, E2F1 Transcription Factor, E2F4 Transcription Factor
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